Neonatal seizures in preterm infants: A systematic review of mortality risk and neurological outcomes from studies in the 2000's

Introduction: Neonatal seizures (NS) are associated with increased mortality and risk of cerebral palsy, epilepsy and intellectual disability. We performed a systematic review with the primary objective to delineate the rate of these outcomes following NS in preterm infants from studies published in the 2000s and the secondary objective to identify risk factors. Methods: Inclusion criteria: original articles published between 1/1/2000 and 12/31/2018, written in English, evaluating newborns <= 37 weeks of gestational age and suffering from NS, in which at least one of these was evaluated: epilepsy, cerebral palsy, intellectual disability/developmental delay, normal outcome, death. Results: Twenty-two papers were selected and all were observational, with a retrospective design in 15. Three were population-based and twenty-one have a comparison. It has been found a 22-80 % of mortality, 11.3-38.9 % of epilepsy, 12-84.6 % of cerebral palsy, and 20-42.7 % of intellectual disability/developmental delay rate. An increased risk for all outcomes considered was reported. Risk factors for specific outcomes were provided by a minority of studies. However, inclusion criteria, definition of NS and measured outcomes, follow-up lengths differed considerably between studies. Discussion: Results of the selected studies are only partially comparable or generalizable because of differences in study design. They have a risk for potential biases, although they provide (if analyzed) readily available prognostic factors, easy to apply in clinical practice. Prospective, population-based studies with EEG-defined NS are warranted in order to produce evidence-based guidance for management of preterm newborns with seizures.